A fine balance between neuronal excitation and inhibition governs the physiological state of the brain. It has been hypothesized that when this balance is lost as a result of excessive excitation or reduced inhibition, pathological states such as epilepsy emerge. Decades of investigation have shown this to be true in vitro. However, in vivo evidence of an emerging imbalance during the “latent period” between the initiation of injury and the expression of the first spontaneous behavioral seizure has not been demonstrated.
“Balanced” networks in the brain have been proposed to account for a large variety of observations of cortical activity, including the representation of sensory information, decision making and sleep and motor control [7]. A loss of balance in the neuronal network activity has been associated with the emergence of a number of neurological diseases including Parkinson's [15], Autism [18], Schizhophrenia [22], and Tourette's syndrome [20]. Epilepsy, a neurological disorder of the brain in which patients suffer from recurrent seizures, is associated with an imbalance in the activity of excitatory and inhibitory populations of neurons in the brain, in favor of the former, leading to an abnormal hyper-synchronous state of the brain [4]. A number of in vitro studies have demonstrated the mechanism of this hyper-excitability at the synaptic level [8,11]. However, the functional implication of these synaptic changes leading to the progression of the brain to an epileptic state following brain injury in an in vivo system is still unknown.
Epilepsy is the propensity to have seizures and is one of the most common serious neurological conditions, affecting 0.4% to 1.0% of the world population [24]. EEG recordings usually demonstrate interictal discharges (population spikes, sharp waves) over the hippocampal formation [25]. One of the major points of confusion in understanding the pathophysiology of epilepsy is the differentiation of a seizure from the interictal discharges. A seizure is a transient paroxysm of excessive discharges of neurons in the cerebral cortex causing a discernable change in behavior. Brief synchronous activity of a group of neurons leading to a population spike shares some mechanisms with seizure generation; spikes should, however, be recognized as a distinct phenomenon [26].
Spikes corresponding to both excitatory and inhibitory synaptic activities are significant features of network changes during epileptogenesis [27,28,29]. There remained, therefore, a need to further understand specific changes in excitatory and inhibitory synaptic balance and their relationship to epileptogenesis.